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Full-Text Articles in Medicine and Health Sciences
Impact Of Clinical And Pharmacogenetic Variables On The Risk Of Fluoropyrimidine-Related Adverse Events Within Ontario, Theodore J. Wigle
Impact Of Clinical And Pharmacogenetic Variables On The Risk Of Fluoropyrimidine-Related Adverse Events Within Ontario, Theodore J. Wigle
Electronic Thesis and Dissertation Repository
Severe life-threatening adverse events are a major limitation of fluoropyrimidine chemotherapy, these events are disastrous for patients and costly to the healthcare system. Identifying patients at high risk for developing adverse events would allow for preventive dose reduction, improving patient outcomes and reducing healthcare cost. This thesis uses data pulled from provincial databases to quantify the adverse event burden of fluoropyrimidines in Ontario. We found that 31% of Ontario patients treated with fluoropyrimidine systemic chemotherapy developed a severe adverse event that requires acute medical care. Patients that required acute medical therapy were significantly costlier to the public system averaging an …
Overcoming Innate And Acquired Therapy Resistance By Targeting Dna Repair In Human Cancer Cells, Mateusz Rytelewski
Overcoming Innate And Acquired Therapy Resistance By Targeting Dna Repair In Human Cancer Cells, Mateusz Rytelewski
Electronic Thesis and Dissertation Repository
Genomic instability and a high mutation rate lead to heterogeneity in human tumors. Mathematical modelling predicts that these characteristics promote acquired resistance to cytotoxic and targeted therapies, by increasing the likelihood that resistant subpopulations exist at the start of treatment (and promoting the accumulation of de novo resistance mutations during treatment). As a result, genome plasticity promotes increased fitness on the population level, but individual tumor cells must nonetheless maintain a level of DNA integrity that allows for continued survival, particularly in the context of DNA-damaging therapy (which DNA repair counteracts). Thus, DNA repair proteins are a source of innate …